Research in this laboratory is centered around solution studies on the structure and dynamics of proteins, protein-protein complexes and protein-nucleic acid complexes using multidimensional NMR spectroscopy, and on the development and application of novel NMR and computational methods to aid in these studies. Particular emphasis is being placed on complexes involved in signal transduction and transcriptional regulation, and on AIDS and AIDS-related proteins. Recent accomplishments include the extension of the applicability of the NMR method to structures larger than 40 kDa, including the determination of the solution structures of the complete 44 kDa trimeric ectodomain of SIV gp41 and the 40 kDa phosphoryl transfer complex between enyzme I and HPr of the bacterial phosphotransferase (PTS)system. Other systems whose structures have recently been solved include the phosphoryl transfer complex of enzyme IIA(glucose)and HPr of the PTS pathway, complexes of the transcription factors GATA-1, AREA, HMG-I/Y and MEF2A with DNA, complexes of wild-type SRY (the male sex determining factor) and a sex reversal mutant of SRY with DNA, the anti-HIV protein cyanovirinin monomeric and domain-swapped dimeric forms, the cellular factor BAF which is responsible for protecting retroviral DNAfrom autointegration, and the N- and C-terminal domains of HIV integrase. Examples of methodological developments include thep anoply of 3D and 4D heteronuclear NMR experiments that have been developed at the NIH and are essential for studying larger proteins whose overlapping resonances pose a formidable problem; methods that make use of anisotropy of the alignment tensor (e.g. residual dipolar couplings measured on macromolecules dissolved in dilute liquid crystalline media such as the nematic phases ofrod-shaped virus particles) or the diffusion tensor (for highly non-spherical molecules) to provide long-range orientational information that is not available from other NMR parameters that rely entirely on close spatial proximity of atoms; and the development of fast and efficient algorithms for the analysis of NMR spectra and for the computation of three-dimensional structures based on all available experimental NMR restraints. Very recent developments include the use of rigid modyminimization and constrained/restrained simulated annealing to accurately dock protein-protein complexes on the basis of intermolecular NOE and dipolar coupling data.